SUMMARY The Proteomics Core will employ cutting-edge proteomics technologies to help address mechanistic questions proposed by the four JHM Udall Center research projects regarding the pathogenesis of Parkinson's disease (PD). The methodologies available through the Proteomics Core provide efficient and sensitive strategies to identify and quantify PD-associated changes in the samples obtained from both disease models and human patients. Thus, we anticipate that proteomic findings generated by the Proteomics Core will help elucidate specific protein-based cellular mechanisms that correlate with PD pathogenesis, identifying novel pathogenic proteins, signaling nodes and protein PTMs with strong association to PD. To this end, the Proteomics Core will provide innovative and traditional mass spectrometry (MS)-based approaches to facilitate the identification and quantification of proteins and their major post-translational modifications (PTMs) including phosphorylation, ubiquitylation and acetylation in the context of diseases. The Core has a wide breadth of expertise in discovery as well as targeted quantitative proteomics methods and strategies. This includes stable isotope labeling by amino acids in cell culture (SILAC) labeling, stable isotope labeling in mammals (SILAM), tandem mass tags (TMT) labeling, filter-aided sample preparation (FASP) based protein extraction and digestion, peptide fractionation methods such as basic reverse-phase liquid chromatography (bRPLC) and strong cation exchange (SCX), chemical and affinity-based PTM-enrichment methods, high-resolution high- accuracy mass spectrometry analysis for global proteomic profiling, targeted quantitation strategies including Multiple Reaction Monitoring (MRM), and bioinformatics and computational tools for the interpretation of even large-scale datasets. The combination of these high-end technologies offers powerful tools to address the proposed research questions of the JHM Udall Center. The overall goal of the Proteomics Core (Core D) is to use state-of-the-art mass spectrometry-based proteomics to facilitate the discovery and validation of protein molecules implicated in PD pathogenesis, providing support to all proposed basic science projects within this Udall Center and to the broader Morris K. Udall scientific community involved in PD research.